Sepsis affects more than 750,000 patients annually in the United States and has a mortality rate of from 30 to 65%, which makes it the tenth most common cause of death in the U.S. The risk of sepsis is found to be inversely related to age. Sepsis accounts for 60 to 80% of childhood deaths in the developing world. As a result of its prevalence, hospital visits for sepsis or septicemia increased from 621,000 in the year 2000 to 1,141,000 in 2008. In economic terms, total costs for treating sepsis increased by an average of 11.9% each year between 1997 and 2008, adjusted for inflation, and amounted to $14.6 billion in the U.S. in 2008 and currently exceed $17 billion. In addition to other hospital treatments, over 2.5 million patients are admitted annually to ICUs for sepsis with the costs per individual ICU case adding $5,000 or more per day to total hospital costs and with treatment lasting at least two days and often more than 20 days. Additionally, nearly 50 percent of diagnosed sepsis cases in the U.S. are attributable to hospital-acquired infections (HAIs), which impose a major direct cost on hospitals due to little to no reimbursement from health insurers.
Sepsis is the body's response to infection. This response is characterized by the cardinal signs of inflammation (e.g., vasodilation, leukocyte accumulation, and increased microvascular permeability) occurring in tissues that are remote from the infection. Even a minor infection, such as strep throat or influenza, can trigger sepsis. Sepsis is usually not life-threatening, but complications of sepsis can cause serious illness and death.
Sepsis is a general term describing immune responses within a continuum from infection to multiple organ dysfunction syndrome. Systemic inflammatory response syndrome (SIRS) is the presence of two or more of abnormal body temperature, heart rate, respiratory rate or blood gas, and white blood cell count, and sepsis is defined as SIRS in response to an infectious process. Severe sepsis is defined as sepsis with sepsis-induced organ dysfunction or tissue hypoperfusion (e.g., manifesting as hypotension, elevated lactate, or decreased urine output). Severe sepsis occurs when a natural immune response to an infection triggers widespread inflammation and blood clotting in tiny vessels throughout the body, which also involves failure of critical organs in the body and can thus lead to death. Finally, septic shock is severe sepsis plus persistently low blood pressure.
Currently, measures for diagnosing sepsis and estimating its severity, prognosis, and the efficacy of therapy include laboratory tests that monitor the evidence of infection; clotting problems; liver or kidney function; oxygen availability; electrolyte levels; and/or cardiovascular, neurologic, or hematologic function. Often these parameters are used to derive illness severity and/or prognosis scores like the Sequential Organ Failure Assessment (SOFA) score. If the site of the infection is not obvious, imaging tests such as X-ray, computerized tomography (CT), ultrasound, or, less commonly, magnetic resonance imaging (MRI), are often performed.
While the existing technologies for treating sepsis have increased success rates of therapies, the management of sepsis remains complicated by inherent difficulties in diagnosis, delayed recognition of organ dysfunction, and a poorly characterized biological phenotype. As such, patient outcomes are compromised and the development of therapies to achieve optimal outcomes (e.g., reduce mortality) are hampered. In addition, use of existing technologies has been limited by an inability to select patients who will most likely benefit from specific treatments and to titrate dosing and duration appropriately.
Some previous approaches have attempted to address this problem using pharmacogenomics to predict drug response in sepsis patients. However, this approach has had limited success due to inconsistencies and limited understanding of the biological indications predictive of successful treatment. Thus, there is a growing need for biomarkers that can indicate both the responsiveness of a patient to a drug and how to titrate the dosage appropriately for a patient.